Cotranscriptional demethylation induces global loss of H3K4me2 from active genes inArabidopsis

Abstract

Based on studies of animals and yeasts, methylation of histone H3 lysine 4 (H3K4me1/2/3, for mono-, di-, and tri-methylation, respectively) is regarded as the key epigenetic modification of transcriptionally active genes. In plants, however, H3K4me2 correlates negatively with transcription, and the regulatory mechanisms of this counterintuitive H3K4me2 distribution in plants remain largely unexplored. A previous genetic screen for factors regulating plant regeneration identified Arabidopsis LYSINE-SPECIFIC DEMETHYLASE 1-LIKE 3 (LDL3), which is a major H3K4me2 demethylase. Here, we show that LDL3-mediated H3K4me2 demethylation depends on the transcription elongation factor Paf1C and phosphorylation of the C-terminal domain (CTD) of RNA polymerase II (RNAPII). In addition, LDL3 binds to phosphorylated RNAPII. These results suggest that LDL3 is recruited to transcribed genes by binding to elongating RNAPII and demethylates H3K4me2 cotranscriptionally. Importantly, the negative correlation between H3K4me2 and transcription is disrupted in the ldl3 mutant, demonstrating the genome-wide impacts of the transcription-driven LDL3 pathway to control H3K4me2 in plants. Our findings implicate H3K4me2 in plants as chromatin memory for transcriptionally repressive states, which ensures robust gene control.

A CPF-like phosphatase module links transcription termination to chromatin silencing

“…2021). Similarly, the Arabidopsis FLD paralog LDL3 has been recently reported to work co-transcriptionally to remove H3K4me2 (Mori et al . 2023).…”

“…Available genome-wide data shows FLD binding correlates with actively transcribed genes and elongating RNA Pol II CTD phosphorylated at Ser2 or Ser5 (Inagaki et al 2021). Similarly, the Arabidopsis FLD paralog LDL3 has been recently reported to work co-transcriptionally to remove H3K4me2 (Mori et al 2023). RNA Pol II occupancy in the Arabidopsis genome often shows peaks near transcription termination sites (TTS), potentially linked to slow co-transcriptional termination events (Wu et al 2016, Zhou et al 2023.…”